JP7420827B2 - 抗il-36r抗体製剤 - Google Patents
抗il-36r抗体製剤 Download PDFInfo
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- JP7420827B2 JP7420827B2 JP2021552832A JP2021552832A JP7420827B2 JP 7420827 B2 JP7420827 B2 JP 7420827B2 JP 2021552832 A JP2021552832 A JP 2021552832A JP 2021552832 A JP2021552832 A JP 2021552832A JP 7420827 B2 JP7420827 B2 JP 7420827B2
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KR102666920B1 (ko) | 2015-04-15 | 2024-05-20 | 아납티스바이오, 아이엔씨. | 인터루킨 36 수용체(il-36r)에 대한 항체 |
CN113543772A (zh) | 2019-03-08 | 2021-10-22 | 勃林格殷格翰国际有限公司 | 抗il-36r抗体制剂 |
CA3188382A1 (en) * | 2020-07-17 | 2022-01-20 | Boehringer Ingelheim International Gmbh | Anti-il-36r antibodies for the treatment of neutrophilic dermatoses |
CN112094349B (zh) * | 2020-11-04 | 2021-02-09 | 上海华奥泰生物药业股份有限公司 | 靶向于白介素36r的抗体及其制备方法和应用 |
WO2022166977A1 (zh) * | 2021-02-08 | 2022-08-11 | 上海普铭生物科技有限公司 | 抗人il-36r抗体及其应用 |
KR20230154455A (ko) | 2021-03-04 | 2023-11-08 | 베링거 인겔하임 인터내셔날 게엠베하 | Gpp의 치료를 위한 방법 |
JP2024518536A (ja) * | 2021-05-12 | 2024-05-01 | アナプティスバイオ インコーポレイティッド | 抗体組成物 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002504907A (ja) | 1997-06-13 | 2002-02-12 | ジェネンテク,インコーポレイテッド | 抗体製剤 |
JP2007524602A (ja) | 2003-04-04 | 2007-08-30 | ジェネンテック・インコーポレーテッド | 高濃度抗体及びタンパク質製剤 |
US20120121580A1 (en) | 2009-07-28 | 2012-05-17 | Merck Sharp & Dohme Corp. | Methods for producing high concentration lyophilized pharmaceutical formulations |
JP2015500633A (ja) | 2011-11-16 | 2015-01-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 抗il−36r抗体 |
JP2018512157A (ja) | 2015-04-15 | 2018-05-17 | アナプティスバイオ インコーポレイティッド | インターロイキン36受容体(il−36r)に対する抗体 |
Family Cites Families (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4419446A (en) | 1980-12-31 | 1983-12-06 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant DNA process utilizing a papilloma virus DNA as a vector |
NZ201705A (en) | 1981-08-31 | 1986-03-14 | Genentech Inc | Recombinant dna method for production of hepatitis b surface antigen in yeast |
US4601978A (en) | 1982-11-24 | 1986-07-22 | The Regents Of The University Of California | Mammalian metallothionein promoter system |
US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
DD266710A3 (de) | 1983-06-06 | 1989-04-12 | Ve Forschungszentrum Biotechnologie | Verfahren zur biotechnischen Herstellung van alkalischer Phosphatase |
US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
US4965199A (en) | 1984-04-20 | 1990-10-23 | Genentech, Inc. | Preparation of functional human factor VIII in mammalian cells using methotrexate based selection |
GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
WO1990003430A1 (en) | 1988-09-23 | 1990-04-05 | Cetus Corporation | Cell culture medium for enhanced cell growth, culture longevity and product expression |
FR2646437B1 (fr) | 1989-04-28 | 1991-08-30 | Transgene Sa | Nouvelles sequences d'adn, leur application en tant que sequence codant pour un peptide signal pour la secretion de proteines matures par des levures recombinantes, cassettes d'expression, levures transformees et procede de preparation de proteines correspondant |
US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
WO1994004188A1 (en) | 1992-08-21 | 1994-03-03 | Genentech, Inc. | Method for treating an lfa-1-mediated disorder |
DK0669836T3 (da) | 1992-11-13 | 1996-10-14 | Idec Pharma Corp | Terapeutisk anvendelse af kimære og radioaktivt mærkede antistoffer og humant B-lymfocytbegrænset differentieringsantigen til behandling af B-cellelymfom |
US5595756A (en) | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
US5888809A (en) | 1997-05-01 | 1999-03-30 | Icos Corporation | Hamster EF-1α transcriptional regulatory DNA |
DE69836082T2 (de) | 1997-08-01 | 2007-05-10 | Schering Corp. | Membranproteine aus säugetierzellen; verwandte reagentien |
US6416973B1 (en) | 1997-08-01 | 2002-07-09 | Schering Corporation | Nucleic acids encoding mammalian cell membrane protein MDL-1 |
AU2001247616B2 (en) | 2000-04-11 | 2007-06-14 | Genentech, Inc. | Multivalent antibodies and uses therefor |
AU2003282667A1 (en) | 2002-10-03 | 2004-04-23 | Large Scale Biology Corporation | Multimeric protein engineering |
US20070041905A1 (en) | 2005-08-19 | 2007-02-22 | Hoffman Rebecca S | Method of treating depression using a TNF-alpha antibody |
US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
AU2007294909A1 (en) | 2006-09-08 | 2008-03-20 | Amgen Inc. | IL-1 family variants |
JP2010526066A (ja) | 2007-04-23 | 2010-07-29 | シェーリング コーポレイション | 抗mdl−1抗体 |
EP2176294B1 (en) | 2007-06-29 | 2015-05-20 | Merck Sharp & Dohme Corp. | Uses of mdl-1 antagonists |
KR20110048536A (ko) | 2008-08-28 | 2011-05-11 | 와이어쓰 엘엘씨 | 자가면역 질병에서 il-22, il-17 및 il-1 패밀리 시토킨의 용도 |
EP2473527B1 (en) * | 2009-09-03 | 2016-11-30 | Ablynx N.V. | Stable formulations of polypeptides and uses thereof |
JP5937523B2 (ja) | 2010-03-01 | 2016-06-22 | サイトダイン インコーポレイテッドCytoDyn, Inc. | 濃縮されたタンパク質製剤およびその使用 |
JO3533B1 (ar) * | 2012-01-23 | 2020-07-05 | Regeneron Pharma | تركيبات ثابته تحتوي على مضادات حيوية مقاومة لـ ang2 |
CA2882771C (en) | 2012-08-24 | 2021-02-23 | Novartis Ag | Nep inhibitors for treating diseases characterized by atrial enlargement or remodeling |
JP2018507202A (ja) | 2015-02-13 | 2018-03-15 | サノフイ | モノクローナル抗体のための安定的な液体製剤 |
CN107921967B (zh) | 2015-08-05 | 2021-06-01 | 福特全球技术公司 | 用于车辆的客户驾驶模式 |
EP3601350A1 (en) | 2017-03-27 | 2020-02-05 | Boehringer Ingelheim International GmbH | Anti il-36r antibodies combination therapy |
WO2019177888A1 (en) | 2018-03-14 | 2019-09-19 | Boehringer Ingelheim International Gmbh | Use of anti-il-36r antibodies for treatment of generalized pustular psoriasis |
JP2021517577A (ja) | 2018-03-14 | 2021-07-26 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 炎症性腸疾患の処置のための抗il−36r抗体の使用 |
WO2020136101A1 (en) | 2018-12-27 | 2020-07-02 | Boehringer Ingelheim International Gmbh | Anti-il-36r antibodies for treatment of palmoplantar pustulosis |
CN113543772A (zh) | 2019-03-08 | 2021-10-22 | 勃林格殷格翰国际有限公司 | 抗il-36r抗体制剂 |
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002504907A (ja) | 1997-06-13 | 2002-02-12 | ジェネンテク,インコーポレイテッド | 抗体製剤 |
JP2007524602A (ja) | 2003-04-04 | 2007-08-30 | ジェネンテック・インコーポレーテッド | 高濃度抗体及びタンパク質製剤 |
US20120121580A1 (en) | 2009-07-28 | 2012-05-17 | Merck Sharp & Dohme Corp. | Methods for producing high concentration lyophilized pharmaceutical formulations |
JP2015500633A (ja) | 2011-11-16 | 2015-01-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 抗il−36r抗体 |
JP2018512157A (ja) | 2015-04-15 | 2018-05-17 | アナプティスバイオ インコーポレイティッド | インターロイキン36受容体(il−36r)に対する抗体 |
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TW202100141A (zh) | 2021-01-01 |
AU2020238676A1 (en) | 2021-09-16 |
US20230372480A1 (en) | 2023-11-23 |
CA3132917A1 (en) | 2020-09-17 |
CN113543772A (zh) | 2021-10-22 |
WO2020185479A1 (en) | 2020-09-17 |
JP2024020372A (ja) | 2024-02-14 |
US20200282053A1 (en) | 2020-09-10 |
MX2021010783A (es) | 2021-09-30 |
KR20210137520A (ko) | 2021-11-17 |
IL286100A (en) | 2021-10-31 |
US11730812B2 (en) | 2023-08-22 |
EP3934617A1 (en) | 2022-01-12 |
EA202192405A1 (ru) | 2022-01-13 |
JP2022524502A (ja) | 2022-05-06 |
BR112021016198A2 (pt) | 2021-11-03 |
CL2021002331A1 (es) | 2022-06-17 |
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